The present invention relates generally to the field of methods and medical devices for modulating cardiac muscle contractility and more specifically to apparatus and methods for determining the parameters of delivery of excitable tissue controller (ETC) signals under a variety of cardiac conditions.
Excitable tissue controllers (ETCs) are devices which modulate the activity of excitable tissues by application of non-excitatory electrical stimulation to the excitable tissue through suitable electrodes in contact with the tissue. For example, ETC devices may be used, inter alia, to increase or decrease the contractility of cardiac muscle in vitro, in vivo and in situ., as disclosed in detail in PCT application, International Publication Number WO 97/25098 to Ben-Haim et al., titled xe2x80x9cELECTRICAL MUSCLE CONTROLLERxe2x80x9d, incorporated herein by reference. Other methods and applications of ETC devices are disclosed in PCT applications commonly-assigned to the assignee of the present application, International Publication Number WO 98/10828, titled xe2x80x9cAPPARATUS AND METHOD FOR CONTROLLING THE CONTRACTILITY OF MUSCLESxe2x80x9d to Ben Haim et al., incorporated herein by reference, International Publication Number WO 98/10829, titled xe2x80x9cDRUG-DEVICE COMBINATION FOR CONTROLLING THE CONTRACTILITY OF MUSCLESxe2x80x9d to Ben Haim et al., incorporated herein by reference and International Publication Number WO 98/10830, titled xe2x80x9cFENCING OF CARDIAC MUSCLESxe2x80x9d to Ben Haim et al., incorporated herein by reference, International Publication Number WO 98/10831 to Ben Haim et al., titled xe2x80x9cCARDIAC OUTPUT CONTROLLERxe2x80x9d, incorporated herein by reference.
Further applications of the ETC including devices combining cardiac pacing and cardiac contractility modulation are disclosed in PCT Application, International Publication No. WO 98/10832, titled xe2x80x9cCARDIAC OUTPUT ENHANCED PACEMAKERxe2x80x9d to Ben Haim et al., co-assigned to the assignee of the present application. Such ETC devices function by applying non-excitatory electrical field signals of suitable amplitude and waveform, appropriately timed with respect to the heart""s intrinsic electrical activity to selected cardiac segments. The contraction of the selected segments can be modulated to increase or decrease the stroke volume of the heart. The timing of the ETC signals must be carefully controlled since application of the ETC signal to the myocardium at inappropriate times may be arrhythmogenic. The ETC signals must therefore be applied to the selected cardiac segment within a defined time interval during which the selected cardiac segment will not be stimulated by the ETC signals.
As disclosed in International Publication No. WO 98/10832, the ETC signals may be timed relative to a trigger signal which is also used as a pacing trigger, or may be timed relative to locally sensed electrogram signals.
U.S. Patent Application to Mika et al., Ser. No. 09/276,460, Titled xe2x80x9cAPPARATUS AND METHOD FOR TIMING THE DELIVERY OF NON-EXCITATORY ETC SIGNALS TO A HEARTxe2x80x9d, filed Mar. 25, 1999 and assigned to the common assignee of the present application, the entire specification of which is incorporated herein by reference, discloses a method for timing the delivery of non-excitatory ETC signals to a heart using, inter alia, an alert window period for reducing the probability of delivering an improperly timed ETC signal to the heart due to spurious detection of noise or ectopic beats.
U.S. patent application Ser. No. 09/328,068 to Mika et al., filed Jun. 8, 1999, assigned to the common assignee of the present application, titled xe2x80x9cAPPARATUS AND METHOD FOR COLLECTING DATA USEFUL FOR DETERMINING THE PARAMETERS OF AN ALERT WINDOW FOR TIMING DELIVERY OF ETC SIGNALS TO A HEART UNDER VARYING CARDIAC CONDITIONSxe2x80x9d, now U.S. Pat. No. 6,223,072, the entire specification of which is incorporated herein by reference, discloses, inter alia, apparatus and methods for collecting data from a patient""s heart. The collected data is processed to obtain a data set which may be used in an ETC device for dynamically setting the parameters of an alert window used for detecting a depolarization event to trigger the delivery of ETC signals to the heart.
U.S. patent application to Mika et al., filed Jun. 23, 1999, Ser. No. 09/338,649, assigned to the common assignee of the present application, titled xe2x80x9cAPPARATUS AND METHOD FOR SETTING THE PARAMETERS OF AN ALERT WINDOW USED FOR TIMING THE DELIVERY OF ETC SIGNALS TO A HEART UNDER VARYING CARDIAC CONDITIONSxe2x80x9d, the entire specification of which is incorporated herein by reference, discloses, inter alia, apparatus and methods for using the data set obtained in U.S. patent application Ser. No. 09/328,068, now U.S. Pat. No. 6,223,072, to Mika et al., referenced hereinabove, for dynamically setting the parameters of an alert time window on a beat by beat basis.
These methods take into account changes in the velocity of propagation of the depolarization wave in the myocardium caused by various cardiac conditions such as pacing of the heart, prior delivery of ETC signals to the myocardium and the beat to beat cycle length (which is indicative of the instantaneous heart rate).
ETC devices effect their influence on the electrochemical/electromechanical dynamics of the tissue through electrical currents delivered to the tissue after it has been stimulated and while it is undergoing active depolarization and repolarization.
However, when attempting to control the contractility of the heart using ETC devices, currents forced through the tissue past the effective refractory period (ERP) may be arrhythmogenic.
Typically, in ETC therapy the duration of the effective refractory period and other parameters of interest such as, inter alia, the action potential duration, the dispersion of repolarization and the activation velocity are estimated under physician supervision during or after the implantation of an implanted ETC device, or after the implantation of electrodes in the patient""s heart and the connection of the implanted electrodes to a non-implantable ETC device disposed outside the patient""s body. Such devices are disclosed, inter alia, in U.S. patent applications Ser. Nos. 09/276,460 and 09/328,068 to Mika et al. and in U.S Patent Application to Mika et al., filed Jun. 23,1999, cited hereinabove. The ERP and the other parameters of interest may then be periodically estimated during follow-up visits of the patient
Unfortunately, since the refractory period of the myocardium may change as a function of various of factors such as, inter-alia, the state of the tissue, the level of circulating hormones, such as, but not limited to cathecholamines, the presence and level of pharmacological agents, artificial cardiac stimulation (e.g. pacing), as well as the previous application of ETC signals, a-priori assessment of the duration of the ERP may not be possible.
Moreover, even if it was possible to assess a mean duration of the ERP for some of the above mentioned cardiac conditions, this only represents an average value which may not be valid for each individual cardiac beat cycle, since the ERP duration value may still fluctuate for individual beats occurring under similar cardiac conditions.
Furthermore, certain pathological conditions such as myocardial ischemia, tachycardia and premature ventricular contractions may result in gradual or even abrupt changes in the cardiac action potential parameters which may result in respective gradual or abrupt changes in the ERP duration, Such changes may increase the probability of delivery of ETC signals in the vulnerable time period outside of the ERP duration, unduly increasing the risk of induced arrhythmia.
Another problem which may be encountered during delivery of cardiac ETC therapy, is that the efficacy of the therapy may change as a result of changes in the cardiac action potential duration (APD). This stems from the fact that the ETC signal effectiveness may vary as a function of the timing of the ETC signal delivery within the non vulnerable portion of the cardiac action potential.
There is therefore provided, in accordance with a preferred embodiment of the present invention, a method for automatically controlling the delivery of excitable tissue control signals to a heart of a patient. The method includes the steps of, determining an estimated action potential duration value from at least one cardiac action potential related signal sensed at a first cardiac site of the heart, processing the estimated action potential duration value to obtain at least one excitable tissue control signal parameter, and using the at least one parameter to control the delivery of one or more excitable tissue control signals to a second cardiac site of the heart after the time of occurrence of the at least one cardiac action potential related signal of the step of determining.
Furthermore, in accordance with a preferred embodiment of the present invention, the cardiac action potential related signal is a close bipolar electrogram signal.
Furthermore, in accordance with a preferred embodiment of the present invention, the close bipolar electrogram signal includes a first signal component representing the differentiated upstroke of the fast depolarization phase of a cardiac action potential and a second signal component representing the differentiated fast repolarization phase of the cardiac action potential, and the step of determining includes determining a first time point at which the amplitude of the first signal component first crosses a first threshold value, determining a second time point at which the amplitude of the second signal component first crosses a second threshold value, and obtaining the estimated action potential duration value by determining the value of the time interval between the second time point and the first time point.
Furthermore, in accordance with a preferred embodiment of the present invention, the close bipolar electrogram signal also includes a third signal component comprising an electrical artifact induced by the delivery of an excitable tissue control signal to the second cardiac site within the duration of the at least one cardiac action potential. The method further comprises the step of processing the close bipolar electrogram signal to reduce or eliminate the third signal component.
Furthermore, in accordance with a preferred embodiment of the present invention, the third signal component is reduced or eliminated by using a method selected from signal blanking and active signal canceling.
Furthermore, in accordance with a preferred embodiment of the present invention, the close bipolar electrogram signal includes a first signal component representing the differentiated upstroke of the fast depolarization phase of a cardiac action potential and a second signal component representing the differentiated fast repolarization phase of the cardiac action potential, and the step of determining includes the steps of determining a first time point at which the amplitude of the first signal component first crosses a first threshold value going in a first direction, determining a second time point at which the amplitude of the second signal component first crosses a second threshold value going in a second direction, and obtaining the estimated action potential duration value by determining the value of the time interval between the second time point and the first time point.
Furthermore, in accordance with a preferred embodiment of the present invention, the cardiac action potential related signal is monophasic action potential signal.
Furthermore, in accordance with a preferred embodiment of the present invention, the at least one cardiac action potential related signal is a monophasic action potential signal.
Furthermore, in accordance with a preferred embodiment of the present invention, the monophasic action potential signal includes a sharp leading edge related to the fast depolarization phase of a cardiac action potential and has a maximal amplitude value, and the step of determining includes the steps of determining a first time point at which the amplitude of the sharp leading edge first crosses a first threshold value, determining the maximal amplitude value, determining a second time point at which the amplitude value of the monophasic action potential signal is equal to a fraction of the maximal amplitude value, and obtaining the estimated action potential duration value by determining the value of the time interval between the second time point and the first time point.
Furthermore, in accordance with a preferred embodiment of the present invention, the monophasic action potential signal also includes an artifact component representing an electrical artifact induced by the delivery of an excitable tissue control signal to the second cardiac site within the duration of the at least one cardiac action potential, and the method further includes the step of processing the monophasic action potential signal to reduce or eliminate the artifact component.
Furthermore, in accordance with a preferred embodiment of the present invention, the artifact component is reduced or eliminated by using a method selected from signal blanking and active signal canceling.
Furthermore, in accordance with a preferred embodiment of the present invention, the monophasic action potential signal includes a sharp leading edge related to the fast depolarization phase of a cardiac action potential and has a maximal amplitude value, and the step of determining includes the steps of high pass filtering the monophasic action potential signal to obtain a high pass filtered signal, processing the high pass filtered signal to determine a first time point at which the amplitude of the high pass filtered signal first crosses a first threshold value, low pass filtering the monophasic action potential signal to obtain a low pass filtered signal, processing the low pass filtered signal to determine the maximal amplitude value thereof, determining a second time point at which the amplitude value of the low pass filtered signal is equal to a fraction of the maximal amplitude value, and obtaining the estimated action potential duration value by determining the value of the time interval between the second time point and the first time point.
There is further provided, in accordance with a preferred embodiment of the present invention, apparatus for automatically controlling the delivery of excitable tissue control signals to a heart of a patient. The apparatus includes means for determining an estimated action potential duration value from at least one cardiac action potential related signal sensed at a first cardiac site of the heart, means for processing the estimated action potential duration value to obtain at least one excitable tissue control signal parameter, and means for using the at least one parameter to control the delivery of one or more excitable tissue control signals to a second cardiac site of the heart after the time of occurrence of the at least one cardiac action potential related signal of the step of determining.
There is further provided, in accordance with a preferred embodiment of the present invention, Apparatus for automatically controlling the delivery of excitable tissue control signals to a heart of a patient. The apparatus includes an excitable tissue control unit for delivering the excitable tissue control signals to a first site of the heart, an action potential duration determining unit operatively connected to the excitable tissue control unit for receiving action potential related signals sensed at a second site of the heart, determining an estimated action potential duration value from at least one of the action potential related signals, computing at least one excitable tissue control signal parameter and controlling the delivery at least one of the excitable tissue control signals based on the at least one excitable tissue control signal parameter. The apparatus further includes a power source for energizing the excitable tissue control unit and the action potential duration determining unit.
Furthermore, in accordance with a preferred embodiment of the present invention, the action potential duration determining unit includes, a close bipolar electrogram sensing unit for sensing close bipolar electrogram signals at the second site of the heart, a digitizing unit operatively connected to the close bipolar electrogram sensing unit for digitizing the close bipolar electrogram signals sensed by the close bipolar electrogram sensing unit to provide digitized close bipolar electrogram signals, and a microprocessor unit operatively connected to the digitizing unit and the excitable tissue control unit, for receiving the digitized close bipolar electrogram signals, determining an estimated action potential duration value from at least one of the digitized close bipolar electrogram signals, computing at least one excitable tissue control signal parameter from the estimated action potential duration value and controlling the delivery of at least one of the excitable tissue control signals based on the at least one excitable tissue control signal parameter.
Furthermore, in accordance with a preferred embodiment of the present invention, the at least one of the action potential related signals includes at least one cardiac close bipolar electrogram signal, and the action potential duration determining unit includes, a close bipolar electrogram sensing unit for sensing close bipolar electrogram signals at the second site of the heart, an action potential duration determining circuit operatively connected to the close bipolar electrogram sensing unit for receiving the close bipolar electrogram signals, processing the close bipolar electrogram signals to provide estimated action potential duration values corresponding to the close bipolar electrogram signals, and a microprocessor unit operatively connected to the action potential duration determining circuit and to the excitable tissue control unit, for receiving the estimated action potential duration values, computing at least one excitable tissue control signal parameter from at least one of the estimated action potential duration values and controlling the delivery of at least one of the excitable tissue control signals based on the at least one excitable tissue control signal parameter.
Furthermore, in accordance with a preferred embodiment of the present invention, the closed bipolar electrogram sensing unit includes a differential amplifier connectable to a pair of electrodes for sensing the close bipolar electrogram signals.
Furthermore, in accordance with a preferred embodiment of the present invention, the action potential duration determining circuit includes a first band pass filter operatively connected to the output terminal of the differential amplifier and adapted to preferentially pass a first frequency range corresponding to a first high frequency component of the close bipolar electrogram signals and to produce a first filtered signal, a second band pass filter operatively connected to the output terminal of the differential amplifier and adapted to preferentially pass a second frequency range corresponding to a second low frequency component of the close bipolar electrogram signals and to produce a second filtered signal, a first tunable threshold circuit operatively connected to the output terminal of the first band pass filter for generating a first trigger signal when the filtered signal crosses a first threshold value, a second tunable threshold circuit operatively connected to the output terminal of the second band pass filter for generating a second trigger signal when the second filtered signal crosses a second threshold value, and an edge activated binary counter operatively connected to the first tunable threshold circuit and to the second tunable threshold circuit for receiving and processing the first trigger signal and the second trigger signal to provide an output signal representing an estimated action potential duration value.
Furthermore, in accordance with a preferred embodiment of the present invention, the action potential duration determining unit includes, a monophasic action potential sensing unit for sensing monophasic action potential signals at the second site of the heart, a digitizing unit operatively connected to the monophasic action potential sensing unit for digitizing the monophasic action potential signals sensed by the monophasic action potential sensing unit to provide digitized monophasic action potential signals, and a microprocessor unit operatively connected to the digitizing unit and the excitable tissue control unit for receiving the digitized monophasic action potential signals, determining an estimated action potential duration value from at least one of the digitized monophasic action potential signals, computing at least one excitable tissue control signal parameter from the estimated action potential duration value and controlling the delivery of at least one of the excitable tissue control signals based on the at least one excitable tissue control signal parameter.
Furthermore, in accordance with a preferred embodiment of the present invention, the microprocessor is adapted to receive the digitized monophasic action potential signal and to obtain therefrom a time value usable as the approximate starting time point of the cardiac action potential corresponding with the currently sensed monophasic action potential signal.
Furthermore, in accordance with a preferred embodiment of the present invention, the digitized monophasic action potential signal also includes an artifact component representing an electrical artifact induced by the delivery of an excitable tissue control signal to the second cardiac site within the duration of sensing the monophasic action potential signal, and the microprocessor unit is adapted for processing the digitized monophasic action potential signal to reduce or eliminate the artifact component.
Furthermore, in accordance with a preferred embodiment of the present invention, the at least one excitable tissue control signal parameter computed by the microprocessor unit is selected from the delay between the detection of a cardiac action potential and the initiation of an excitable tissue control signal, the duration of the excitable tissue control signal, the intensity of the excitable tissue control signal, the waveform of the excitable tissue control signal, the polarity of the excitable tissue control signal and any combination thereof.
Furthermore, in accordance with a preferred embodiment of the present invention, the at least one excitable tissue control signal parameter is the delay between the detection of a cardiac action potential and the initiation of the excitable tissue control signal, and the microprocessor unit is adapted for computing the delay by multiplying the estimated action potential duration value by a first coefficient xcex1 to obtain a first computed value, and by adding a first constant C1 to the first computed value.
Furthermore, in accordance with a preferred embodiment of the present invention, the first coefficient xcex1 is empirically determined for the patient.
Furthermore, in accordance with a preferred embodiment of the present invention, the at least one excitable tissue control signal parameter is the duration of an excitable tissue control signal, and wherein the duration is computed by multiplying the estimated action potential duration value by a second coefficient xcex2 to obtain a second computed value, and by adding a second constant C2 to the second computed value.
Furthermore, in accordance with a preferred embodiment of the present invention, the second coefficient xcex2 is empirically determined for the patient.
Furthermore, in accordance with a preferred embodiment of the present invention, the monophasic action potential signal includes a sharp leading edge related to the fast depolarization phase of a cardiac action potential and has a maximal amplitude value. The microprocessor unit is adapted to determine a first time point at which the amplitude of the sharp leading edge first crosses a first threshold value, determine the maximal amplitude value, determine a second time point at which the amplitude value of the monophasic action potential signal is equal to a fraction of the maximal amplitude value, and obtain the estimated action potential duration value by determining the value of the time interval between the second time point and the first time point.
Furthermore, in accordance with a preferred embodiment of the present invention, the second time point is the time point at which the amplitude value of the monophasic action potential signal is equal to 10% of the maximal amplitude value and the estimated action potential duration value is the MAP90 value.
Furthermore, in accordance with a preferred embodiment of the present invention, the at least one of the action potential related signals includes at least one cardiac monophasic action potential, and the action potential duration determining unit includes, a monophasic action potential sensing unit for sensing monophasic action potential signals at the second site of the heart, an action potential duration determining circuit operatively connected to the monophasic action potential sensing unit for receiving the monophasic action potential signals and processing the monophasic action potential signals to provide estimated action potential duration values corresponding to the monophasic action potential signals, and a microprocessor unit operatively connected to the action potential duration determining circuit and to the excitable tissue control unit for receiving the estimated action potential duration values, computing at least one excitable tissue control signal parameter from at least one of the estimated action potential duration values and controlling the delivery of at least one of the excitable tissue control signals based on the at least one excitable tissue control signal parameter.
Furthermore, in accordance with a preferred embodiment of the present invention, the microprocessor is adapted to compute the average estimated action potential duration by using a moving average program selected from a weighted moving average program and a non-weighted moving average program.
Furthermore, in accordance with a preferred embodiment of the present invention, the moving average program is implemented using an implementation method selected from a finite impulse response implementation method and an infinite impulse response implementation method.
Furthermore, in accordance with a preferred embodiment of the present invention, the microprocessor unit is adapted to disable the delivery of at least one of the excitable tissue control signals to the second site of the heart if the estimated action potential duration value is smaller than a minimal acceptable action potential duration value.
Furthermore, in accordance with a preferred embodiment of the present invention, the first cardiac site is in the vicinity of the second cardiac site.
Finally, in accordance with a preferred embodiment of the present invention, the first cardiac site and the second cardiac site are located in or about the left ventricle of the heart.